There is evidence that omega-3 fatty acids are useful in the prevention and treatment of heart disease. There is also some evidence that they might be important for cognitive function or useful as a treatment for depression.

There are three important omega-3 fatty acids:

ALA - alpha-linolenic acid; found in a wide range of foods

EPA - eicosapentaenoic acid; found mainly in fish

DHA - docosahexaenoic acid; found mainly in fish and seaweed

The body can convert ALA into EPA and DHA. ALA is efficiently converted to EPA, but it may require large amounts of ALA to produce optimal amounts of DHA. A small amount of recent evidence has raised a concern that large amounts of ALA could be harmful to the eyes over the long term.

Introduction to the Omega-3 Fatty Acids

For our purposes, there are three important omega-3 fatty acids:

ALA is a short chain (18 carbon) omega-3 fatty acid. It is found in small amounts in animal flesh,
in very small amounts in a variety of plant products, and in relatively large amounts in soy,
walnuts, canola oil, flaxseeds and their oil, hempseed oil, camelina oil, and chia seed oil.
The human body cannot make its own ALA - it must be obtained through the diet.

EPA is a long chain (20 carbon) omega-3 fatty acid. It is found mostly in fatty fish, in small amounts
in eggs, and in very small amounts in seaweed. Some EPA is converted into series 3 eicosanoids
which can reduce blood clotting, inflammation, blood pressure, and cholesterol. The human body
can produce EPA out of ALA and out of DHA.

DHA is a long chain (22 carbon) omega-3 fatty acid. It is found mostly in fatty fish, in small amounts
in eggs, and in very small amounts in seaweed. It is a major component of the gray matter of the
brain, and also found in the retina, testis, sperm, and cell membranes. The body can convert EPA into DHA.

All three of these omega-3 fatty acids may prevent heart arrhythmias, though ALA has been studied
the least in clinical trials.

A chart showing the conversion pathways for the omega-3 and omega-6 fatty acids can be found in
this article.

Heart Disease

As of May 2012, the American Heart Association was still basing its omega-3 fatty acid recommendations on its 2002 position paper, Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease (31) recommends that adults "Eat a variety of (preferably oily) fish at least twice a week. Include oils and foods rich in alpha-linolenic acid (flaxseed, canola, and soybean oils; flaxseed and walnuts)."

Whether fish or fish oil substantially reduces the risk of cardiovascular disease is somewhat controversial and a topic beyond the scope of this article. The Linus Pauling Institute at Oregon State University provides a good review of the literature in their article, Essential Fatty Acids. Vegetarians already have about a 24% lower risk of heart disease (5), and it is not clear that more EPA or DHA could further benefit them to any significant degree. The main concern is with the possibility of cognitive problems in vegetarians due to long-term DHA deficiency.

Omega-3s and Depression

A 2007 meta-analysis from Taiwan (8) and a 2006 review from Canada (9) found that supplementation with EPA and DHA improved depression, but a 2006 review from the UK (10) found that it did not.

According to the USDA nutrient database, a medium egg contains about 2 mg of EPA and 16 mg of DHA. That provides lacto-ovo vegetarians with very small amounts of dietary EPA and DHA. Vegans who are not supplementing have an intake of essentially no EPA and DHA.

Three studies have listed the amount of ALA intake for vegetarians (who were presumably not purposefully adding rich sources of ALA to their diets). See Table 3.

It appears that vegetarians meet about 50 to 60% of the daily ALA recommendations without special diet planning.

Vegans and vegetarians have been shown in many studies to have lower levels of long chain omega-3 fatty acids (EPA and DHA) than meat eaters. Table 4 shows the results of some of these studies. The general trend is that lacto-ovo vegetarians and vegans have lower levels of EPA and DHA in their blood.

One exception is the 2010 UK study in which vegan women had, on average, higher DHA levels than even the fish-eaters. There were only 5 vegan women making the finding unlikely to be statistically significant; the average DHA level was 286 µmol/l with a standard deviation of 211 µmol/l. That means that one or two of the vegan women had very high levels of DHA but some had very low. The researchers didn't assess how long the vegans had been following their diet.

Lower blood levels of EPA and, especially, DHA in vegetarians doesn't necessarily mean that they have lower levels of EPA or DHA in other tissues, but it is something to be careful about until more is known.

Effects of Low EPA and DHA on Vegetarians

One of the main things that long chain omega-3 fatty acids do, particularly EPA, is reduce blood clotting which protects against heart attacks. There have been some differences noted in blood clotting between vegetarians and meat-eaters.

A 1999 Chile study (18) found that vegetarians had significantly more platelets (242,000 per ul) than non-vegetarians (211,000 per ul) and a shorter bleeding time (4.5 vs. 7.3 min).

In a follow-up 2000 Chile study (4), vegetarians were given 700 mg EPA and 700 mg DHA for 8 weeks. EPA went from .2 to 1.8% and DHA went from 1.1 to 3.0%. Some clotting factors did change, but bleeding time remained higher at 5 1/2 minutes.

In a 1992 UK study (16), only one of eight platelet aggregation parameters in the men (but not the women) was different from the non-vegetarians. Bleeding times were similar.

Thus, of two studies that looked at these factors, vegetarians were doing worse than meat-eaters in one, but were basically the same in the other.

In terms of depression and cognition, there has been no research on omega-3s and vegetarians, but Joel Fuhrman, MD, has a private practice seeing many long-term vegans and has observed some older vegan men with very low DHA levels and cognitive problems, so there is reason to be prudent regarding DHA in older vegans, especially men (link).

To bolster this theory, here is an excerpt from a paper on DHA and Alzheimer's Disease:

In his 2006 review article, anthropologist John H. Langdon argues that DHA is not an essential nutrient for the brain development of infants. Pregnant women efficiently convert ALA to DHA and fetuses and infants are able to receive DHA that is released from the mother's fat tissue and provided through the umbilical cord or breast milk. In cases of very low levels of DHA from the mother, infants can utilize other fatty acids for brain tissue which can later be replaced by DHA (32).

A 1994 study measured the DHA levels in umbilical cords of 32 infants born to vegetarian mothers compared to omnivores (30). The analysis revealed no relationship between the proportions of DHA in plasma or cord artery phospholipids and the birth weight or head circumference of the infants.

In another studying comparing breast milk, cow's milk formula with DHA, soy formula with DHA, and soy formula without DHA, infants who ate soy formula without DHA had indications of slower parasympathetic development, though still within the normal range (87).

Many children have been raised vegan without supplementing with DHA, or even extra ALA, and, to our knowledge, most of these children have developed well (link).

To be safe, and until more is known, parents of vegetarian children could supplement their diets with DHA at 200 mg every 2 or 3 days.

The traditional way that vegetarians were encouraged to raise EPA and DHA levels was by increasing ALA and decreasing linoleic acid (LA), a short chain omega-6 fatty acid. The body can convert ALA into EPA and DHA. The enzymes that do this conversion also convert LA into longer chain omega-6s, and can be saturated with omega-6s if there is a lot in the diet. If they are saturated with omega-6s, they are not able to convert omega-3s.

Most vegetable oils are high in omega-6s and vegetarians tend to get plenty in their diets. A 1981 UK study (17) showed that the dietary ratio of omega-6 to omega-3 fats was 16 for vegans and 6 for meat-eaters. A 1992 UK study (16) showed a ratio of 15.8 for vegan men vs. 10.2 for meat-eating men, and 18.3 for vegan women vs. 8.2 for meat-eating women. An ideal ratio is thought be about 3 or 4.

To deal with this problem, in the late 90s and 00s, vegetarian health professionals recommended increasing ALA intake and decreasing LA intake. Unfortunately, there are no long-term studies looking at vegetarians' blood EPA and DHA after following these recommendations. But we do have some related studies.

A 1999 study (Table 5) of 17 vegetarian men in Australia (15), aged about 26 to 42 years old, showed that four weeks of 3.7 g of ALA per day (the equivalent of about 1.5 teaspoons of flaxseed oil) did not significantly increase the percentages of EPA or DHA in the blood. The same study showed that four weeks of 15.4 g of ALA (the equivalent of about 6.5 teaspoons of flaxseed oil) did increase EPA levels, but still did not increase DHA levels. There was no change in clotting factors (bleeding time was not reported).

A 2000 study from The Netherlands (20) showed no change in EPA or DHA after 4 weeks of 2.0 g of ALA per day in 9 vegans aged 20 to 60 years old. By adding that much ALA, the ratio of dietary ALA:LA went from 13.7 to 6.7.

A 2014 study from the USA (38) put the same group of lacto-ovo vegetarians on three different daily regimens for 8 weeks each: 1 oz of walnuts (3.0 g of ALA), 1 regular egg (110 mg DHA), and 1 fortified egg (~500 mg DHA, 40 mg EPA, 1 g ALA). The ratio of n-6:n-3 was 6:1 in the walnut phase and DHA levels did not increase.

In a 1981 UK study (17), 4 vegans aged 26 to 37 years took 6.5 g of ALA per day for 2 weeks. They had some increase in EPA and DHA levels. See Table 6.

A 1992 study from India (21), in which 5 vegetarians aged 25 to 40 years old were given 3.7 g of ALA per day, showed an increase in EPA and DHA, and a reduction in LDL cholesterol and blood aggregation. See Table 7.

In summary, it appears that 3.7 grams of ALA per day is needed for vegetarians to see an effect in blood DHA percentages in the short-term. But, there isn't any research in which participants were asked to cut their LA intake at the same time that they increased ALA intake. So we don't really know if doing that would boost DHA levels in the blood or other tissues.

In order to figure out what the ALA to EPA/DHA conversion rates are for vegetarians, it may be particularly important to stick with studies that use actual vegetarians rather than meat-eaters who might have a dietary source of EPA and DHA. But because there is a lack of long term studies on vegetarians, we should look at some of the research on meat-eaters.

There have been many studies on meat-eaters' conversion rates, and for the most part they have shown good conversion of ALA to EPA, but very little to DHA. Because small amounts or short terms do not appear to be promising, I will limit my review to two studies that used larger amounts and longer time periods.

A 2008 study on meat-eaters from Canada (22) who took 1.2, 2.4, and 3.6 g ALA per day for 12 weeks resulted in an increase in the percentage of EPA in red blood cell fatty acids for the 2.4 and 3.6 ALA groups, but no increases in DHA. This study used an "intention to treat" method, which means that subjects who did not comply with the regimen were still included in the results. I'd like to know the results only for the people who stuck with the regimen, but there was little information given on the level of compliance.

A 1999 study on Japanese (23) elderly subjects gave them 3 g ALA per day and reduced the omega-6 to omega-3 ratio to 1:1. After 3 months, there was no difference in EPA and DHA levels, but after 10 months, EPA levels had risen from 2.5 to 3.6% of serum lipids, and DHA levels rose from 5.4 to 6.4% (both findings statistically significant).

Welch et al. (24) reported that non-fish eaters (both vegetarians and meat-eaters) convert ALA to long chained omega-3s at a slightly greater rate than do meat-eaters, so conversion rates of vegetarians might be greater than these studies on meat-eaters show.

In summary, it appears that 3 g (equivalent of about 1-1/2 teaspoons of flaxseed oil) per day of ALA cannot increase blood percentages of DHA in three months time, but can increase blood percentages in 10 months time, assuming intake of omega-6 is low.

A 2014 study from the USA (39) gave 46 vegans, selected on the basis of having low omega-3 status, a daily dose of 172 mg DHA and 82 mg EPA for 4 months. Percent of total red blood cell fatty acids went from about .6% to .8% for EPA and from about 2.3% to 3.25% for DHA.

In a 2009 review paper (29), Sanders describes a placebo-controlled, randomized trial from the UK in which 39 vegan men supplemented with 200 mg of DHA per day for 3 months and increased the proportion of DHA in plasma by 50% (from about .8 to 1.3% of plasma lipids).

A 2006 double-blinded, placebo-controlled, trial from Germany (35) gave 87 female and 27 male vegetarians 940 mg of DHA per day for 8 weeks. Plasma phospholipids went from 2.8% yo 7.3% DHA.

A 2006 single-blinded, randomized, placebo-controlled trial from Taiwan (36) gave 27 postmenopausal vegetarian women 2,140 mg of DHA per day for 6 weeks. LDL fatty acid composition went from 1.4% to 3.7% DHA.

A 1996 double-blinded trial from Canada (2) gave 1,620 mg of DHA to 12 male and 12 female vegetarians per day for 6 weeks. Serum phospholipids went from 2.4% to 8.3% DHA, and platelet phospholipids increased from 1.2% to 3.9%. A 1997 study from the same researchers (1), and same dose and length, increased serum phospholipids from 2.1% to 7.1% DHA, and increased serum platelet phospholipids from 1.1% to 3.4% in vegetarians.

What levels of percentage of fatty acids should vegans aim for? If you average the percentages in the paragraph above (multiplied by the number of participants), you get an average of 2.0%. And if you average the vegans' DHA levels, you get 1.1%.

200 mg per day raised vegan DHA levels .6%. 300 mg can then be expected to raise vegans' DHA levels .9%, taking them from an average of 1.1% to 2.0%. It thus seems reasonable to recommend 300 mg per day for the average vegan to match the same level as the average omnivores. But since it is not clear that vegans need DHA levels equal to omnivores, taking 200-300 mg every 2 to 3 days could be adequate insurance while not costing nearly as much.

Anecdotal reports have found some older vegans to have very low DHA levels, so supplementing with 200 - 300 mg per day is prudent for people over 60.

A 60 year old, male, long time vegan forwarded his fatty acid lab reports to me. In August 2012 his EPA levels were .3% and DHA was 1.0% (of fatty acids in blood). He had been using "a lot of" canola oil but it apparently wasn't increasing his EPA and DHA levels. After six months of daily supplementation of 320 mg DHA plus 130 mg of EPA (one capsule of Ovega-3 vegan supplement), his EPA levels went to 1.0% (about average for omnivores) and DHA to 4.8% (towards the higher average range for omnivores). It appears that this regimen was adequate.

Retroconversion of DHA to EPA

A 1996 Canadian study (2) showed an 11 - 12% conversion rate of DHA to EPA after 6 weeks of 1,620 mg of DHA in vegetarians. See Table 9 for more details showing that EPA levels increased.

A 1997 Canadian study (1) of vegetarians and meat-eaters showed a conversion rate of 9.4% of DHA to EPA from a dose of 1,620 mg DHA per day for 6 weeks, with no differences between groups.

A 2000 trial from Chile (4) gave vegetarians 700 mg EPA and 700 mg DHA for 8 weeks. DHA went from 1.1 to 3.0%. EPA went from .2 to 1.8%

A 1996 French study (3) fed three people 123 mg of DHA one time and found a conversion rate to EPA of 1.4%.

I could not find any other studies looking at DHA amounts less than 700 mg per day.

In recent years, there have been numerous studies that have shown benefits of a high ALA intake and a few that have shown potential problems. Here is a quick review of those areas.

Heart Disease

A meta-analysis of five prospective studies of ALA intake published in 2004 (7) suggested that high ALA intake was associated with reduced risk of fatal heart disease (relative risk 0.79, .60-1.04). This finding was not quite statistically significant. The average highest level of intake was 2.0 g per day versus the lowest of .8 g per day.

Prostate Cancer

In contrast to the findings on heart disease which have been fairly consistent in favor of a modest benefit, ALA intake and blood levels have been associated with the risk of prostate cancer in a number of studies, and not associated in a number of other studies. Reviewing this material is beyond the scope of this article, but if you are interested in reading more details, a good review starts on p. 80 of Chapter 6: Flax and the Prevention of Cancer from FLAX - A Health and Nutrition Primer (Fourth Edition, 2007) published by the Flax Council. The following paragraph does a good job in summarizing the literature:

Otherwise, there are too many inconsistencies among the research findings to be confident that any one fatty acid contributes to cancer development in humans. These inconsistencies apply to most fatty acids, not just ALA. For instance, among the studies summarized in Tables 17 and 18, LA was associated with an increase in prostate cancer risk in 2 studies, had no association with prostate cancer in 7 studies and had an inverse relationship with prostate cancer in 5 studies.

I would not be worried about increasing the risk of prostate cancer with an intake of 2.0 g per day of ALA, the amount that is associated with a reduced risk of heart disease.

When examined by study type (ie, retrospective compared with prospective or dietary ALA compared with tissue concentration) or by decade of publication, only the 6 studies examining blood or tissue ALA concentrations revealed a statistically significant association. With the exception of these studies, there was significant heterogeneity and evidence of publication bias. After adjustment for publication bias, there was no association between ALA and prostate cancer (RR: 0.96; 95% CI: 0.79, 1.17).

And a 2010 meta-analysis found that subjects who consumed more than 1.5 g/day of ALA had a significant decreased risk of prostate cancer (0.95, 0.91-0.99) compared to those who ate less (34).

Eyesight

There have been four studies looking at age-related eye damage and ALA. For age-related macular degeneration, the study using a better marker of ALA status showed it to be protective. For cataracts-related markers, the studies show that a higher intake of ALA is associated with an increased risk. Skip details.

Age-Related Macular Degeneration

A 2001 analysis (14) of men and women in the Nurse's Health Study over age 50 found that those in the highest fifth of ALA intake (about 1.5 g per day) had an increased risk of age-related macular degeneration (AMD) compared to the lowest intake (about .77 g per day; 1.41, 1.00-1.98). Total fat, saturated, monounsaturated, and trans fat were all associated with an increase in AMD. In contrast, the highest intakes of DHA tended to be protective. The fourth quintile of animal fat was also associated with a statistically significant increase in AMD (1.36, 1.03 - 1.79). The authors state:

To evaluate further the association with linolenic acid, the major food sources of this fatty acid were examined (Table 5). These foods provided 38% of linolenic acid intake in women and 46% in men at baseline. Of the food sources of linolenic acid, intake of beef, pork, or lamb as a main dish appeared strongly positively related to AMD. More than 1 serving/wk of beef, pork, or lamb as a main dish was associated with a 35% increased risk of AMD compared with <3 servings/mo (pooled RR: 1.35; 95% CI: 1.07, 1.69). A high intake of margarine was also significantly related to an increased risk of AMD. Because these food items were also major contributors of trans unsaturated fat, we adjusted further for quintiles of trans unsaturated and other fats in models with linolenic acid; the relation with linolenic acid was slightly attenuated but remained significant (Table 4). Other high-fat foods were not associated with risk of AMD (data not shown).

In contrast, a 2013 study from France (6) found that higher ALA levels in the blood were associated with a lower risk of late AMD (.62, .43-.88 per 1 standard deviation increase in plasma ALA). The results were adjusted for age, gender, smoking, educational level, physical activity, HDL, trigylcerides, CFH Y402H, ApoE4, and ARMS2 A69S polymorphisms, and follow-up time.

I would consider plasma levels in the blood a more accurate measure of ALA status than intakes, because intakes are much harder to measure independently of other fatty acids. Given that this study found that higher levels of ALA were associated with a decreased risk of late AMD, it provides some confidence that the finding from the Nurse's Health Study was a matter of confounding.

Although the study from France used a better marker for ALA status, it was conducted by people who have received compensation from a variety of pharmaceutical companies, was smaller in number and shorter in duration than the Nurse's Health Study, and measured only late-AMD. It would be nice to see a few more studies before drawing any strong conclusions.

Cataracts

A 2005 analysis (12) of a group of women from the Nurse's Health Study found that both the highest intakes of ALA and LA were associated with an increase in lens opacity, which can lead to cataracts. Interestingly, neither total fat, animal fat, vegetable fat, saturated fat, nor trans fats were associated with an increase in lens opacity. For ALA, the risk ratio was 2.2 (1.2, 4.5) for about 1.26 g compared to .86 g per day.

A 2007 analysis (13) of the same group found that the highest category of ALA intake (about 1.26 g per day) was linked to a 16% increase in eye lens nuclear density compared to the lowest category (about .84 g per day) over five years. In this case, no other fat category was associated with an increase, including total, animal, vegetable, saturated, monounsaturated, polyunsaturated, trans, LA, arachidonic acid, or long chain omega-3s.

ALA and Eyesight: Conclusion

In the case of age-related macular degeneration, it seems unlikely that raw ALA from plant foods can cause a problem. Unfortunately the analyses of lens opacity and nuclear density did not show any correlation with animal fat and so it is hard to dismiss all of these findings as simply confounding. Until more research is preformed, it might be prudent not to consume large amounts of ALA.

The studies finding ALA to be linked with eye problems were all done on only one population by one group of researchers, measuring intakes rather than blood levels. I consider it likely that further studies will show inconsistencies and until plant and/or uncooked sources of ALA are examined, I am skeptical that uncooked, plant sources of ALA are harmful to the eye.

According to the Canola Council, canola oil should be safe for use in cooking. Based on the results of the above studies on eye lens damage, make sure you use low heat and limited cooking times when cooking with canola oil until more is
known about ALA and eye damage.

DHA and Prostate Cancer

In July of 2013, a study surfaced suggesting the DHA supplementation might cause prostate cancer. This concern is probably unwarranted, though if you are at a high risk for prostate cancer you might want to err on the lower side of the recommendations here. More details can be read in the article, DHA Supplements and Prostate Cancer.

Summary of Omega-3 Benefits and Concerns

What we know about ALA is summarized in Table 11.

If it weren't for the (small chance) for potential eye problems, I would suggest either adding 3 g of ALA per day or taking DHA supplements. Because of the eye issues, that much ALA is not worth the risk when DHA supplements are available. I would still recommend adding about .5 g of ALA per day for its own benefits for heart disease and to help increase EPA levels. If using such small amounts of uncooked, plant sources of ALA the risk to the eyes should be minimal.

If you are getting the recommended ALA and DHA, EPA should not be a problem. Fish contain about twice as much DHA as EPA (27), so it's not unusual to get more DHA than EPA in the diet. But it is okay to get a supplement with EPA and DHA in it. If you get a DHA supplement with EPA in it, choose one with at least 200 mg of DHA per serving; I have no recommendations for how much EPA it should contain.